Elders in general suffer from multiple co-occurring chronic conditions. Previous studies using some general markers of Allostatic Load (AL) to measure cumulative biological risk - MacArthur studies on successful aging - have shown that only those persons with the highest levels of AL experienced significantly greater declines in functioning. The major goal of this project is to provide a thorough examination of the concept of AL as a measure of cumulative biological burden in a group of elderly Puerto Rican living in the Greater Boston Area, Several mechanisms of activation and inactivation of the stress response have evolved to deal with the daily threats to survival. Repeated small stressors or a major sustained stressor over a period of time may have detrimental effects on health. We argue that the persistence of inflammatory stimuli over time represents the biological background favoring the susceptibility to age-related diseases/disabilities. Interestingly, socioeconomic status and level of education play a key role in these declines; the poor suffer earlier mortality and worse health than the wealthier and/or better educated. Therefore, there is a need to identify biological markers that can signal the impact on health of living environment, work, relationships, community, education and practice of health promoting or health damaging diet and exercise. From a cohort of 1600 Hispanic elderly subjects, 500 will be engaged in assessing, in addition to the tests described in project #1, the role of inflammatory markers on functional declines associated with AL. The central hypothesis of the project is that elevated blood markers of inflammation driven by the events in the immune system in response to AL and poor nutritional status will be associated with high risk of functional declines and cognitive impairment in the context of a more prevalent chronic disease. Two specific aims will be pursued to accomplish the objectives of the proposal: 1).Quantify the levels of pro-inflammatory cytokines, specifically IL-1beta, TNFalpha, IL-6 and IL-10, C-reactive protein, chemokines (MCP-1), adhesion molecules (ICAM-1) and prostaglandins PGE2 and PGI2; and 2). Determine the immune cell response following exposure to LPS stimuli by quantifing the expression of pro-inflammatory cytokines (IL-1beta, TNFalpha and IL-6 ) and the relationship between the degree of reponse and prevalence of cytokine gene polymorphisms in this population.